Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury

Benedikt Brommer, Miao He (), Zicong Zhang, Zhiyun Yang, Jessica C. Page, Junfeng Su, Yu Zhang, Junjie Zhu, Emilia Gouy, Jing Tang, Philip Williams, Wei Dai, Qi Wang, Ryan Solinsky, Bo Chen () and Zhigang He ()
Additional contact information
Benedikt Brommer: Harvard Medical School
Miao He: Harvard Medical School
Zicong Zhang: Harvard Medical School
Zhiyun Yang: Harvard Medical School
Jessica C. Page: Harvard Medical School
Junfeng Su: Harvard Medical School
Yu Zhang: Harvard Medical School
Junjie Zhu: Harvard Medical School
Emilia Gouy: Harvard Medical School
Jing Tang: Harvard Medical School
Philip Williams: Harvard Medical School
Wei Dai: Harvard Medical School
Qi Wang: Harvard Medical School
Ryan Solinsky: Spaulding Rehabilitation Hospital
Bo Chen: University of Texas Medical Branch
Zhigang He: Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-20980-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20980-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-20980-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().